In the late 1980s, a diagnosis of chronic myelogenous leukemia (CML) was invariably fatal. A remarkable therapy called imatinib specifically targets the genetic alteration responsible for CML, the BCR-ABL tyrosine kinase fusion. In yesterday’s plenary session, “Imatinib as a Paradigm of Targeted Cancer Therapies,” the AACC 2018 Wallace H. Coulter Lectureship Award winner, Brian Druker, MD, discussed his research that revolutionized CML treatment from chemotherapy that indiscriminately poisons cells to laser-focused therapy.
As an oncologist and researcher, Druker, director of the Oregon Health and Sciences University Knight Cancer Institute, and a Howard Hughes Medical Investigator, was “struck by the toxicity that occurred as a result of therapy.” His research focused on finding a different type of treatment. “To me, it seemed there had to be a better way and the way forward was to better understand what drove the growth of cancer cells and to use this knowledge to develop more effective and less toxic therapies,” Druker said.
During clinical trials in the 1990s, patients with CML who were treated with imatinib experienced 100% response rates with minimal side effects. Recognizing this breakthrough discovery, the FDA approved imatinib in record time in 2001 for patients with CML. The potency of imatinib as an effective and well-tolerated cancer therapy is best demonstrated by the fact its use has expanded beyond CML treatment and is now FDA-approved for 10 different cancer types.
There is tremendous demand for targeted cancer therapies and leveraging what we’ve learned from imatinib is crucial. “I hope that people can appreciate the incredible depth of scientific discovery that is required to identify optimal therapeutic targets,” Druker noted.
Indeed, clinical laboratories also play a key role in developing and validating tests to determine who should receive targeted therapies, whether treated patients have developed resistance, and which promising therapies can be combined.
Given the awe-inspiring success of imatinib, it was surprising to learn about the uncertainty Druker initially faced. “When I embarked on this journey, there was incredible skepticism that targeted cancer therapies would work,” Druker said. “It was my patients, who desperately needed something better and who put their faith in me, that deserve the credit for fueling my persistence.”
Given the history of CML as a lethal disease, the most compelling evidence of imatinib’s efficacy is that Druker still treats many patients in his clinic today who participated in the clinical trials with imatinib nearly 20 years ago.
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